GRANT=6546041;P01AG The Tissue Core will play a central role in this Program Project by providing well-characterized brain and other tissues to the Research Projects and by continuing to examine novel and atypical cases. These activities are carried out through three Specific Aims. In the First Specific Aim, the Tissue Core will determine presence, type, severity, and anatomic distribution of the structural lesions in tissues from all transgenic mice and other animals. Brain and, when needed, other tissues will be processed for histological, histoblot, and immunohistochemical examinations. Profiles of the histological lesions and maps of scrapie prion protein distribution will be made if necessary. They will be constructed in a way to be comparable to similar data obtained from the human prion diseases that the animal models may match. The Specific Aim 2 deals with human tissues. Well-characterized human brain tissues will be distributed to the Animal Core for inoculation to receptive animals. Similarly, well-characterized human brain tissues will be provided to the Research Projects to validate data obtained from the cell models. Human brains carrying diseases modeled in animals will be examined comparatively with the brains from the animal models. In addition, the Tissue Core will study in detail individual cases that carry atypical or novel forms of prion disease as well as groups of cases of particular interest. An important asset of the Tissue Core is its close interaction with the National Prion Diseases Pathology Surveillance Center which collects tissues from over a hundred cases of prion diseases per year from the entire country. Therefore, the Tissue Core is in the unique position to examine rare and novel cases. In Specific Aim 3, the Tissue Core will continue to collect human cases of prion diseases from other countries as well as animal tissues from other countries as well as the United States. All these tissues will be stored and will continue to be available to all research laboratories in the United States and around the world.